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  • Single doses of THC and cocaine decrease proficiency of impulse control in heavy cannabis users.

    5 February 2018

    BACKGROUND AND PURPOSE: Cannabis is the most popular drug used in the European Union, closely followed by cocaine. Whereas cannabis impairs neurocognitive function in occasional cannabis users, such impairments appear less prominent in heavy users, possibly as a result of tolerance. The present study was designed to assess whether the impairing effects of Δ(9) -tetrahydrocannabinol (THC) in heavy cannabis users would present in a wide range of neuropsychological functions or selectively affect specific performance domains. We also assessed the acute effects of cocaine on neurocognitive functions of heavy cannabis users. EXPERIMENTAL APPROACH: Heavy cannabis users, who had a history of cocaine use (n = 61), participated in a double-blind, placebo-controlled, three-way crossover study. Subjects received single doses of cocaine HCl (300 mg), cannabis (THC μg·kg(-1) ) and placebo, and completed a number of tests measuring impulse control and psychomotor function. KEY RESULTS: Single doses of cannabis impaired psychomotor function and increased response errors during impulsivity tasks. Single doses of cocaine improved psychomotor function and decreased response time in impulsivity tasks, but increased errors. CONCLUSIONS AND IMPLICATIONS: Heavy cannabis users display impairments in a broad range of neuropsychological domains during THC intoxication. Impairments observed in psychomotor tasks, but not in impulsivity tasks, appeared smaller in magnitude as compared with those previously reported in occasional cannabis users. Heavy cannabis users were sensitive to the stimulating and inhibitory effects of cocaine on psychomotor function and impulsivity respectively. The reduction in proficiency in impulse control may put drug users at increased risk of repeated drug use and addiction.

  • Characterizing the cognitive effects of cocaine: a comprehensive review.

    19 February 2018

    Understanding the cognitive sequela of repeated cocaine use is a growing area of research and is crucial to the development of cognitive models of addiction. We systematically reviewed all available placebo-controlled and case-controlled studies on the acute and long-term effects of cocaine on cognitive functioning. In order to compare the magnitude of cognitive effects across cognitive domains we conducted several meta-analyses on a subset of data from long-term effect studies. Studies on acute cocaine administration suggest enhancement of response inhibition and psychomotor speed, while all other domains appear to be unaffected or not investigated adequately. Long-term effects of cocaine show a wide array of deteriorated cognitive functions, indicating that long term cocaine use is characterized by a general cognitive impairment across functions, rather than by specific cognitive deficits. Literature on long-term cocaine effects is more substantial than literature on acute effects. This comprehensive review outlines possible dissociations and similarities of acute vs. long-term cocaine effects in the human brain. Atherosclerosis after cocaine exposure may underlie cognitive dysfunction, suggesting involvement of multiple brain areas. Acute drug studies are important to the future development of addiction models.

  • EEG phenotypes predict treatment outcome to stimulants in children with ADHD.

    19 February 2018

    This study demonstrates that the EEG phenotypes as described by Johnstone, Gunkelman & Lunt are identifiable EEG patterns with good inter-rater reliability. Furthermore, it was also demonstrated that these EEG phenotypes occurred in both ADHD subjects as well as healthy control subjects. The Frontal Slow and Slowed Alpha Peak Frequency and the Low Voltage EEG phenotype discriminated ADHD subjects best from controls (however the difference was not significant). The Frontal Slow group responded to a stimulant with a clinically relevant decreased number of false negative errors on the CPT. The Frontal Slow and Slowed Alpha Peak Frequency phenotypes have different etiologies as evidenced by the treatment response to stimulants. In previous research Slowed Alpha Peak Frequency has most likely erroneously shown up as a frontal theta sub-group. This implies that future research employing EEG measures in ADHD should avoid using traditional frequency bands, but dissociate Slowed Alpha Peak Frequency from frontal theta by taking the individual alpha peak frequency into account. Furthermore, the divergence from normal of the frequency bands pertaining to the various phenotypes is greater in the clinical group than in the controls. Investigating EEG phenotypes provides a promising new way to approach EEG data, explaining much of the variance in EEGs and thereby potentially leading to more specific prospective treatment outcomes.

  • The acute effects of MDMA and ethanol administration on electrophysiological correlates of performance monitoring in healthy volunteers.

    28 January 2018

    RATIONALE: Knowing how commonly used drugs affect performance monitoring is of great importance, because drug use is often associated with compromised behavioral control. Two of the most commonly used recreational drugs in the western world, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and ethanol (alcohol), are also often used in combination. The error-related negativity (ERN), correct-related negativity (CRN), and N2 are electrophysiological indices of performance monitoring. OBJECTIVES: The present study aimed to investigate how ethanol, MDMA, and their co-administration affect performance monitoring as indexed by the electrophysiological correlates. METHODS: Behavioral and EEG data were obtained from 14 healthy volunteers during execution of a speeded choice-reaction-time task after administration of ethanol, MDMA, and combined ethanol and MDMA, in a double-blind, placebo-controlled, randomized crossover design. RESULTS: Ethanol significantly reduced ERN amplitudes, while administration of MDMA did not affect the ERN. Co-administration of MDMA and ethanol did not further impair nor ameliorate the effect of ethanol alone. No drug effects on CRN nor N2 were observed. DISCUSSION: A decreased ERN following ethanol administration is in line with previous work and offers further support for the impairing effects of alcohol intoxication on performance monitoring. This impairment may underlie maladaptive behavior in people who are under influence. Moreover, these data demonstrate for the first time that MDMA does not affect performance monitoring nor does it interact with ethanol in this process. These findings corroborate the notion that MDMA leaves central executive functions relatively unaffected.

  • Long-term effects of left frontal rTMS on EEG and ERPs in patients with depression.

    28 January 2018

    Repetitive transcranial magnetic stimulation (rTMS) treatment for depression has been under investigation in many controlled studies over the last 20 years. Little is known about the neurobiological action of rTMS in patients. We therefore investigated pre- and post-treatment effects on QEEG, ERP's and behavior (BDI and NEO-FFI). rTMS treatment was applied in 8 subjects for an average of 21 sessions to the left Dorsolateral Prefrontal Cortex (left DLPFC). Clients were assessed on a QEEG and Oddball ERP evaluation pre- and post-treatment. Clients were stimulated over the left DLPFC with 10 Hz rTMS (100% MT). Furthermore, rTMS treatment was complimented by psychotherapy. All subjects showed full remission within 20 sessions and there was a significant reduction in depressive symptomatology (BDI score) after 10 and 15 sessions and a clear decrease in the Neuroticism and an increase on the extraversion scale of the NEO-FFI personality questionnaire. Pre- and post-QEEG measurements did not reveal treatment specific effects, but only an indirect right frontal increase in delta power. On the other hand, ERP measures did reveal treatment specific effects by showing an increased positivity in the post-treatment ERP's specifically left frontal. The P2 amplitude demonstrated a significant left frontal increase in amplitude, whereas for the negative N1 and N2 a significant decrease in amplitude was observed. The results of this pilot study demonstrate that rTMS can be a safe and efficacious treatment modality for depression. Furthermore, a specific left frontal increase in positivity for the ERP's was found (increased P2 and decreased N1 and N2 components) most likely related to the rTMS over the left DLPFC. Furthermore, there was no change in the alpha asymmetry lending support to the fact that frontal alpha asymmetry can be considered a trait marker for depression. The findings from this pilot study require future replication with larger sample sizes.

  • DBH -1021C>T and COMT Val108/158Met genotype are not associated with the P300 ERP in an auditory oddball task.

    5 February 2018

    OBJECTIVE: The amplitude and latency of the P300 may be associated by variations in dopaminergic genes. The current study was conducted to determine whether functional variants of the catechol-O-methyltransferase (COMT) and dopamine beta-hydroxylase (DBH) gene were associated with P300 amplitude and latency in an auditory oddball task. METHODS: The P300 ERP was assessed by a two-tone auditory oddball paradigm in a large sample of 320 healthy volunteers. The Val108/158Met polymorphism (rs4680) of the COMT gene and the -1021C>T polymorphism (rs1611115) of the DBH gene were genotyped. P300 amplitude and latency were compared across genotype groups using analysis of variance. RESULTS: There were no differences in demographic characteristics in subjects for genotypic subgroups. No genotype associations were observed for the P300 amplitude and latency on frontal, central and parietal electrode positions. CONCLUSIONS: COMT Val108/158Met and DBH -1021C>T polymorphisms do not show evidence of association with characteristics of the P300 ERP in an auditory oddball paradigm in healthy volunteers. SIGNIFICANCE: We failed to find evidence for the association between dopaminergic enzymatic polymorphisms and the P300 ERP in healthy volunteers, in the largest study undertaken to date.

  • Psychedelic symptoms of cannabis and cocaine use as a function of trait impulsivity.

    29 December 2017

    Trait impulsivity has been linked to addiction in humans. It has been suggested that drug users with high trait impulsivity levels are more sensitive to subjective drug intoxication. This study assessed whether subjective response to drugs differs between drug users with normal or high levels of trait impulsivity. Regular drug users (N = 122) received doses of cocaine HCl, cannabis, and placebo in a three-way crossover study. Their mood, dissociative state, and psychedelic symptoms were measured with subjective rating scales (CADDS, Bowdle, POMS). Trait impulsivity was assessed with the Barratt Impulsiveness Scale. Cannabis increased dissociation and psychedelic state, as well as fatigue, confusion, depression and anxiety, and decreased arousal, positive mood, vigor, friendliness, and elation. Cocaine increased dissociation, psychedelic state, vigor, friendliness, elation, positive mood, anxiety and arousal, while decreasing fatigue. Only a few subjective items revealed a drug × trait impulsivity interaction, suggesting that psychedelic symptoms were most intense in high impulsivity subjects. Trait impulsiveness ratings were negatively correlated with ratings of vigor (r = -.197) and positively correlated with ratings of loss of thought control (r = .237) during cannabis intoxication. It is concluded that a broad association between trait impulsivity and psychedelic subjective drug experience appears to be absent.

  • An investigation of EEG, genetic and cognitive markers of treatment response to antidepressant medication in patients with major depressive disorder: a pilot study.

    28 January 2018

    The aim of this study was to investigate if biomarkers in QEEG, genetic and neuropsychological measures are suitable for the prediction of antidepressant treatment outcome in depression. Twenty-five patients diagnosed with major depressive disorder were assessed twice, pretreatment and at 8-wk follow-up, on a variety of QEEG and neuropsychological tasks. Additionally, cheek swab samples were collected to assess genetic predictors of treatment outcome. The primary outcome measure was the absolute decrease on the HAM-D rating scale. Regression models were built in order to investigate which markers contribute most to the decrease in absolute HAM-D scores. Patients who had a better clinical outcome were characterized by a decrease in the amplitude of the Auditory Oddball N1 at baseline. The 'Met/Met' variant of the COMT gene was the best genetic predictor of treatment outcome. Impaired verbal memory performance was the best cognitive predictor. Raised frontal Theta power was the best EEG predictor of change in HAM-D scores. A tentative integrative model showed that a combination of N1 amplitude at Pz and verbal memory performance accounted for the largest part of the explained variance. These markers may serve as new biomarkers suitable for the prediction of antidepressant treatment outcome.

  • MDMA, cannabis, and cocaine produce acute dissociative symptoms.

    19 February 2018

    Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo-controlled studies were conducted. In Study 1 (N=16), participants received single doses of 25, 50, and 100 mg of MDMA, and placebo. In Study 2 (N=21), cannabis (THC 300 µg/kg), cocaine (HCl 300 mg), and placebo were administered. Dissociative symptoms as measured with the Clinician-Administered Dissociative States Scale (CADSS) significantly increased under the influence of MDMA and cannabis. To a lesser extent, this was also true for cocaine. Dissociative symptoms following MDMA and cannabis largely exceeded those observed in schizophrenia patients, were comparable with those observed in Special Forces soldiers undergoing survival training, but were lower compared with ketamine-induced dissociation. Cocaine produced dissociative symptoms that were comparable with those observed in schizophrenia patients, but markedly less than those in Special Forces soldiers and ketamine users. Thus, MDMA and cannabis can produce dissociative symptoms that resemble dissociative pathology. The study of drug induced dissociation is important, because it may shed light on the mechanisms involved in dissociative psychopathology.